ABSTRACT
Objective To study the effect of simvastatin on the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and β-catenin in myocardial cells of rabbits with chronic heart failure (CHF).Methods Twenty-four male New Zealand rabbits were randomly divided into control group,CHF model group and simvastatin treatment group,with 8 rabbits in each group.The rabbits in CHF model group and simvastatin treatment group were injected with adriamycin (2.0 mg · kg-1) ria ear rein once a week for six weeks,and from the seventh week were injected with adriamycin (1.5 mg · kg-1)once a week for another six weeks to establish the CHF model;the rabbits in control group were injected with the same volume saline.The rabbits in simvastatin treatment group were given simvastatin (1.5 mg · kg-1 · d-1) by intragastric administration at the time point of first injection of adriamycin for 12 weeks;the rabbits in CHF model group and control group were given the same volume saline for 12 weeks.The left ventricular structure and function were determined by color doppler uhrasonography after the modeling.Then the rabbits were sacrificed and the left ventricular walls were taken to observe the changes of myocardial cell structures by hematoxylin-eosin staining.The positive expression rate of PTEN and β-catenin protein was calculated by immunohistochemistry staining.The expression of PTEN and β-catenin mRNA was detected real-time quantitative polymerase chain reaction.Results Compared with the control group,the left ventricular end-systolic dimension (LVESD),left ventricular end-diastolic dimension(LVEDD) were increased and the left ventricular ejection fraction(LVEF) was decreased in the CHF model group and simvastatin treatment group(P ＜ 0.05).Compared with the CHF model group,the LVESD,LVEDD were decreased and the LVEF was increased in the simvastatin treatment group(P ＜ 0.05).The positive expression rate of PTEN protein in myocardial cells of rabbits in control group,CHF model group and simvastatin treatment group was (16.36 ± 0.54) ％,(41.63 + 0.72) ％ and (24.17 ± 0.51) ％ respectively;the positive expression rate of β-catenin protein in myocardial cells of rabbits in control group,CHF model group and simvastatin treatment group was (21.73 ± 0.46)％,(52.26 ±+ 0.72) ％ and (38.42 + 0.56) ％ respectively.The positive expression rates of PTEN and β-catenin protein in myocardial cells of rabbits in CHF model group and simvastatin treatment group were significanlty higher than those in the control group(P ＜ 0.05);the positive expression rates of PTEN and β-catenin protein of myocardial cell in simvastatin treatment group were significantly lower than those in the CHF model group (P ＜ 0.05).The epression of PTEN mRNA and β-catenin mRNA in myocardial cells of rabbits in control group,CHF model group and simvastatin treatment group was 1.91 ± 0.30,4.61 ± 0.71,3.49 ± 0.64 and 1.51 ± 0.21,2.48 ± 0.34,1.51 ±+ 0.25.The expression of PTEN and β-catenin mRNA in myocardial cells of rabbits in CHF model group and simvastatin treatment group were significanlty higher than those in the control group (P ＜ 0.05);the expression of PTEN and β-catenin mRNA in myocardial cells of rabbits in simvastatin treatment group were significantly lower than those in the CHF model group (P ＜ 0.05).Conclusion Simvastatin can inhibit myocardial apoptosis,improve cardiac function of CHF rabbits.It may be related to inhibiting the expression of PTEN and β-catenin.